rs3729992

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000257.4(MYH7):c.-8-25G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 1,610,064 control chromosomes in the GnomAD database, including 4,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 366 hom., cov: 33)

Exomes 𝑓: 0.073 ( 4050 hom. )

Consequence

MYH7
NM_000257.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.792

Publications

4 publications found

Variant links:

Genes affected

MYH7 (HGNC:7577): (myosin heavy chain 7) Muscle myosin is a hexameric protein containing 2 heavy chain subunits, 2 alkali light chain subunits, and 2 regulatory light chain subunits. This gene encodes the beta (or slow) heavy chain subunit of cardiac myosin. It is expressed predominantly in normal human ventricle. It is also expressed in skeletal muscle tissues rich in slow-twitch type I muscle fibers. Changes in the relative abundance of this protein and the alpha (or fast) heavy subunit of cardiac myosin correlate with the contractile velocity of cardiac muscle. Its expression is also altered during thyroid hormone depletion and hemodynamic overloading. Mutations in this gene are associated with familial hypertrophic cardiomyopathy, myosin storage myopathy, dilated cardiomyopathy, and Laing distal myopathy. [provided by RefSeq, May 2022]

MYH7 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
dilated cardiomyopathy 1S
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
hypertrophic cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
MYH7-related skeletal myopathy
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
myopathy, myosin storage, autosomal recessive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
myopathy, myosin storage, autosomal dominant
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
congenital myopathy 7A, myosin storage, autosomal dominant
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Ebstein anomaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hyaline body myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
left ventricular noncompaction
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

MYH7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-23433765-C-A is Benign according to our data. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in CliVar as Benign. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH7	NM_000257.4 link	c.-8-25G>T		intron_variant	Intron 2 of 39	ENST00000355349.4	NP_000248.2	P12883
MYH7	NM_001407004.1 link	c.-8-25G>T		intron_variant	Intron 1 of 38		NP_001393933.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH7	ENST00000355349.4 link	c.-8-25G>T	intron_variant	Intron 2 of 39	1	NM_000257.4	ENSP00000347507.3	P12883
MYH7	ENST00000713768.1 link	c.-8-25G>T	intron_variant	Intron 2 of 40			ENSP00000519070.1
MYH7	ENST00000713769.1 link	c.-8-25G>T	intron_variant	Intron 1 of 38			ENSP00000519071.1

Frequencies

GnomAD3 genomes

AF:

0.0627

AC:

9547

AN:

152210

Hom.:

367

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0283

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.0748

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.0571

Gnomad SAS

AF:

0.0981

Gnomad FIN

AF:

0.0523

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0755

Gnomad OTH

AF:

0.0717

GnomAD2 exomes

AF:

0.0699

AC:

17341

AN:

248174

AF XY:

0.0736

show subpopulations

Gnomad AFR exome

AF:

0.0246

Gnomad AMR exome

AF:

0.0448

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.0563

Gnomad FIN exome

AF:

0.0558

Gnomad NFE exome

AF:

0.0766

Gnomad OTH exome

AF:

0.0804

GnomAD4 exome

AF:

0.0727

AC:

105968

AN:

1457736

Hom.:

4050

Cov.:

AF XY:

0.0740

AC XY:

53669

AN XY:

725392

show subpopulations

African (AFR)

AF:

0.0239

AC:

798

AN:

33412

American (AMR)

AF:

0.0478

AC:

2138

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

2893

AN:

26114

East Asian (EAS)

AF:

0.0379

AC:

1504

AN:

39682

South Asian (SAS)

AF:

0.0982

AC:

8454

AN:

86090

European-Finnish (FIN)

AF:

0.0584

AC:

3082

AN:

52810

Middle Eastern (MID)

AF:

0.0899

AC:

433

AN:

4814

European-Non Finnish (NFE)

AF:

0.0741

AC:

82285

AN:

1109930

Other (OTH)

AF:

0.0728

AC:

4381

AN:

60200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

5019

10038

15057

20076

25095

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3018

6036

9054

12072

15090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0626

AC:

9541

AN:

152328

Hom.:

366

Cov.:

AF XY:

0.0618

AC XY:

4602

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0282

AC:

1173

AN:

41578

American (AMR)

AF:

0.0747

AC:

1144

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

361

AN:

3470

East Asian (EAS)

AF:

0.0574

AC:

297

AN:

5176

South Asian (SAS)

AF:

0.0981

AC:

474

AN:

4830

European-Finnish (FIN)

AF:

0.0523

AC:

555

AN:

10620

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0755

AC:

5136

AN:

68026

Other (OTH)

AF:

0.0705

AC:

149

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

458

917

1375

1834

2292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0705

Hom.:

534

Bravo

AF:

0.0603

Asia WGS

AF:

0.0730

AC:

254

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.7

(source)

DANN

Benign

0.59

PhyloP100

0.79

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over